DESCRIPTION: (Applicant's Abstract) The purpose of the Submacular Surgery Trials (SST) is to evaluate submacular surgical removal of choroidal neovascular lesions secondary to age-related macular degeneration, ocular histoplasmosis, and unknown causes in four randomized clinical trials, each for a different lesion type and presumed etiology. Only one eye (study eye) of each patient is expected to be eligible for one of the SST clinical trials. Patients assigned at random to the control arm will be managed by either observation (no treatment) or laser photocoagulation, depending upon the type of lesion and the findings from earlier clinical trials of treatment of choroidal neovascularization. The primary outcome for each trial will be change in visual acuity from baseline to the two-year examination, with better or same visual acuity as at baseline deemed a successful outcome. The principal secondary outcome will be change in health-related quality of life from baseline to the two-year interview, as assessed using the Medical Outcomes Study SF-36 questionnaire. Other outcomes of particular interest include adverse events, such as repeated surgery or other treatment of the study eye and loss of measurable visual acuity in the study eye. The participating centers will be 50 to 55 clinical centers where patients will be evaluated for eligibility, treated, and followed clinically; the Study Chairman's Office which is responsible for overall leadership and direction of the SST; the SST Coordinating Center which is responsible for providing scientific leadership and logistic support to the SST investigative team; and the SST Photograph Reading Center which is responsible for assessing the ability of the ophthalmologists to identify and enroll eligible patients and to adhere to the treatment protocol. Approximately 1600 patients will be enrolled in the four clinical trials and randomly assigned to one of the two treatment arms of the trial for which eligible by personnel at the SST Coordinating Center. An independent Data and Safety Monitoring Committee will review the data at least twice each year to assess the risks and benefits of surgery. This application is for funding to support the activities of the SST Photograph Reading Center. CENTER TRACK RECORD: The Photographic Reading Center has had extensive experience in serving in this capacity for other similar clinical trials such as the Macular Photocoagulation Study (MPS) and the Roferon-A in Neovascular AMD Study as well as the SST Pilot Study. Much of our understanding of the problem of CNV derives from investigations centered at the Wilmer Photograph Reading Facility. They have contributed in a major way to the definitions of the variety of lesions that may present and their associated prognoses and treatments. Their past experience has no doubt enabled them to define procedures which insure quality in all aspects of the functioning of a reading center. They appreciate the important external and internal procedures critical to the integrity of a study of this kind. These include such issues as development of photographic protocols, training of photographers and ophthalmologists, assessment of photograph quality and interpretation relative to inclusion and exclusion criteria, documentation of treatment adherence to protocol, evaluation of adverse events, evaluation of follow-up photos and archival activities. Internal issues as administration, photographic management and reading, data analysis and reporting, quality assurance are all described fully and give reason to be assured that they will be addressed appropriately. While there are real advantages to having the Reading Center and Study Chairman s Office (as well as the Coordinating Center) at the same institution to foster communication and coordinate effort, there is the possible weakness of proximity leading to a less stringent evaluation of performance. This concern is somewhat mitigated as past experience has shown that collaborative efforts among this group have been admirably productive. INVESTIGATOR(S): Susan Bressler, M.D. would serve as the Principal Investigator of the SST Photograph Reading Center. Her previous experience includes acting a Principal and Co-Investigator for Reading Centers in other NEI-sponsored studies, particularly in the area of macular degeneration. Andrew P. Schachat, M.D. will act as Co-Investigator of the Photograph Reading Center. He has been the P.I. of the Reading Center in three other NEI-sponsored trials and has played important roles as a clinical ophthalmologist in other trials. The individuals identified as Senior Leader, Deborah Phillips, and Photograph Reading Coordinator, Rochelle Cooper, have served for many years in these capacities in other clinical trials. FACILITIES/ADMINISTRATIVE ARRANGEMENTS: The SST Photograph Reading Center is housed in the Wilmer Reading Center of the Retinal Vascular Center, where other reading centers for multi-center clinical trials are housed. It is not clear that dedicated space is available. The Reading Center is administratively distinct from the Coordinating Center. The scientific conduct of the Center is directed by Dr. Susan Bressler and assessed by the Director, Judith Alexander. Regular meetings are held with the Reading Center staff, the Study Chairman s Office, and the Coordinating Center. Communication with the clinical centers will be open and will serve to enhance photography related adherence to protocol and quality and to identify any perceived need for protocol modification. BUDGET NOTE: NEI Staff should evaluate the requested budget in light of their experience with the budget needs of reading centers in other clinical trials. ADMINISTRATIVE NOTE: Awards, if made, are limited to 5 years.